His bundle mapping, pacing, and injection lead

ABSTRACT

A cardiac rhythm management system includes a lead assembly for intracardiac mapping, pacing, and drug delivery. The lead assembly includes an implantable endocardial lead having a proximal end for connection to an implantable cardiac rhythm management device and a distal end for disposal in an intracardiac region. The lead includes a pacing-sensing electrode and a drug delivery device, both located at or near the distal end. A lumen is within and extends throughout the lead, with an opening at or near the proximal end and another opening at or near the distal end. The lumen provides for access to the intracardiac region by a steerable stylet and a hollow needle, one at a time. The steerable stylet allows for electrophysiological mapping of the intracardiac region. The hollow needle allows for delivery of chemical, biochemical, and/or biological substance to the intracardiac region.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related to U.S. patent application Ser. No.10/246,249, “DEVICES AND METHODS TO STIMULATE THERAPEUTIC ANGIOGENESISFOR ISCHEMIA AND HEART FAILURE,” filed on Sep. 18, 2002, assigned toAdvanced Cardiovascular Systems, Inc., and U.S. patent application Ser.No. 10/264,494, “EXTENDABLE AND RETRACTABLE LEAD HAVING A SNAP-FITTERMINAL CONNECTOR,” filed Oct. 4, 2002, now issued as U.S. Pat. No.6.915,169, assigned to Cardiac Pacemakers, Inc., which are herebyincorporated by reference in their entirety.

TECHNICAL FIELD

This document generally relates to cardiac rhythm management systems andparticularly, but not by way of limitation, to such systems including alead assembly for intracardiac electrophysiological mapping, pacing, anddrug delivery.

BACKGROUND

A heart is the center of a person's circulatory system. It includes acomplex electro-mechanical system performing two major pumpingfunctions. The heart includes four chambers: right atrium (RA), rightventricle (RV), left atrium (LA), and left ventricle (LV). The leftportions of the heart, including the LA and LV, draw oxygenated bloodfrom the lungs and pump it to the organs of the body to provide theorgans with their metabolic needs for oxygen. The right portions of theheart, including the RA and RV, draw deoxygenated blood from the bodyorgans and pump it to the lungs where the blood gets oxygenated. Thesemechanical pumping functions are accomplished by contractions of theheart. In a normal heart, the sinoatrial (SA) node, the heart's naturalpacemaker, generates electrical impulses, called action potentials, thatpropagate through an electrical conduction system to various regions ofthe heart to excite the muscular tissues of these regions. Coordinateddelays in the propagations of these electrical impulses in a normalelectrical conduction system cause the various portions of the heart tocontract in synchrony to result in efficient pumping functions. Ablocked or otherwise abnormal electrical conduction system and/or adeteriorated myocardium cause asynchronized contraction of the heart.Consequently, the person suffers from poor hemodynamic performance,including poor pumping efficiency and diminished blood supply that isusable to satisfy the needs for normal metabolism of the organs.

The heart's electrical conduction system includes internodal pathwaysbetween the SA node and the atrioventricular (AV) node, the AV node, theHis bundle (also known as the bundle of His, the AV bundle, and theCommon bundle), and the Purkinje system including the right bundlebranch (RBB) and the left bundle branch (LBB). In the normal heart, theelectrical impulses generated from the SA node are conducted to the AVnode through the internodal pathways. The propagation of the electricalimpulses is delayed in the AV node. The His bundle conducts theelectrical impulses from the AV node to the right bundle branch (RBB)and left bundle branch (LBB). The RBB and LBB then conduct theelectrical impulses to the RV and LV, respectively, through the Purkinjesystem, resulting in the contraction of the ventricles.

Damages or depression of the AV node and/or His bundle, known as AVblock, impairs the AV conduction, i.e., conduction of the electricalimpulses from the RA to the RV and LV. AV block, depending on a degreeor severity, can result in excessive delay in the AV conduction, partialblockage of the AV conduction (only some electrical impulses areconducted to the ventricles), or total blockage of the AV conduction (noelectrical impulse is conducted to the ventricles). AV block can resultfrom, for example, ischemia, acute myocardial infarction, intoxication,and inflammation. Ablation of the AV node, a surgical procedureperformed on patients with atrial fibrillation, also creates totalblockage of the AV conduction.

Pacing therapy can restore cardiac function impaired by AV block. Onemethod is His bundle pacing, i.e., delivery of pacing pulses to the Hisbundle. If conduction system below the AV node remains normal, pacingpulses delivered to the His bundle are conducted through the His bundleand the bundle branches to cause synchronized contraction of theventricles. In addition, pacing of the His bundle prevents itsdegeneration, a pathological process that starts with severe or total AVblock.

His bundle pacing requires locating a pacing site in or about the Hisbundle. Unlike conventional atrial and ventricular pacing sites, whichcan be located by imaging techniques such as fluoroscopy, His bundlecannot be reliably located by imaging. Additionally, chemical,biochemical, and biological therapies may provide further benefits tothe condition of the AV node and/or His bundle, as well as other cardiacregions, in addition to His bundle pacing.

Therefore, there is a need for an improved method and system fordelivering a therapy to the His bundle.

SUMMARY

A cardiac rhythm management system includes a lead assembly forintracardiac mapping, pacing, and drug delivery. The lead assemblyincludes an implantable endocardial lead having a proximal end forconnection to an implantable cardiac rhythm management device and adistal end for disposal in an intracardiac region. The lead includes apacing-sensing electrode and a drug delivery device, both located at ornear the distal end. A lumen is within and extends throughout the lead,with an opening at or near the proximal end and another opening at ornear the distal end. The lumen provides for access to the intracardiacregion by a steerable stylet and a hollow needle, one at a time. Thesteerable stylet allows for electrophysiological mapping of theintracardiac region. The hollow needle allows for delivery of chemical,biochemical, and/or biological substance to the intracardiac region.

In one embodiment, an implantable endocardial lead includes an elongatelead body having a proximal end and a distal end. The lead includes anelectrode for sensing cardiac electrical activities and deliveringpacing pulses, and a drug delivery device for delivering apharmaceutical substance. Both the electrode and the drug deliverydevice are at or near the distal end. A lumen extends throughout thelead body and has one opening at about the proximal end of the lead andanother opening at about the distal end of the lead. The lead is for usewith an implantable cardiac rhythm management device.

In one embodiment, an implantable endocardial pacing lead assemblyincludes a steerable stylet and an implantable lead. The steerablestylet has a stylet distal end and a stylet proximal end. It includes amapping electrode at the stylet distal end, a connector at the styletproximal end, and a conductor electrically coupled between the mappingelectrode and the connector. The implantable lead has an elongate leadbody having a lead proximal end and a lead distal end. It includes anelectrode at or near the lead distal end for sensing cardiac electricalactivities and delivering pacing pulses. A lumen is within and extendsthrough the lead body, with a proximal opening at about the leadproximal end and a distal opening at about the lead distal end. Thelumen accommodates at least a portion of the steerable stylet and allowsthe stylet tip to enter the proximal opening and extend from the distalopening.

In one embodiment, an implantable endocardial pacing lead assemblyincludes a hollow needle and an implantable lead. The hollow needleallows for intracardiac injection of a therapeutic biological substance.It includes a needle tip and a flexible needle body connected to theneedle tip. The implantable lead includes an elongate lead body having alead proximal end and a lead distal end. It includes an electrode at ornear the distal end for sensing cardiac electrical activities anddelivering pacing pulses. A lumen is within and extends through the leadbody, with a proximal opening at about the lead proximal end and adistal opening at about the lead distal end. The lumen accommodates atleast a portion of the needle and allows the needle tip to enter theproximal opening and extend from the distal opening.

In one embodiment, a system providing for access to an intracardiacregion includes an implantable medical device and a lead. Theimplantable medical device includes a pacemaker to deliver pacing pulsesto the intracardiac region. The lead includes an elongate lead body, anelectrode, a drug delivery device, and a lumen. The elongate lead bodyhas a lead proximal end and a lead distal end. The electrode, located ator near the lead distal end, senses cardiac electrical activities fromand delivers pacing pulses to the intracardiac region. The drug deliverydevice, also located at or near the lead distal end, delivers apharmaceutical substance to the intracardiac region. The lumen is withinand extends through the lead body. The lumen has a proximal opening atabout the lead proximal end and a distal opening at about the leaddistal end.

In one embodiment, therapies are delivered to an intracardiac region inor about a His bundle. A pharmaceutical substance, including one or moreagents preventing degeneration of the intracardiac region, is deliveredusing an implantable endocardial pacing lead coupled to an implantablepulse generator. Pacing pulses are also delivered to the intracardiacregion to enhance an effect of the pharmaceutical substance, using theimplantable endocardial pacing lead coupled to the implantable pulsegenerator.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects of the invention will be apparent to persons skilled in the artupon reading and understanding the following detailed description andviewing the drawings that form a part thereof, each of which are not tobe taken in a limiting sense. The scope of the present invention isdefined by the appended claims and their equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, which are not necessarily drawn to scale, like numeralsdescribe similar components throughout the several views. The drawingsillustrate generally, by way of example, but not by way of limitation,various embodiments discussed in the present document. The drawing arefor illustrative purposes only, and are neither to scale noranatomically accurate.

FIG. 1A is an illustration of an embodiment of portions of animplantable unipolar endocardial lead for pacing an intracardiac region.

FIG. 1B is an illustration of an embodiment of portions of animplantable bipolar endocardial lead for pacing an intracardiac region.

FIG. 1C is an illustration of an embodiment of a stylet accessing to theintracardiac region through the implantable endocardial lead of FIG. 1Aor FIG. 1B.

FIG. 1D is an illustration of an embodiment of a needle accessing to theintracardiac region through the implantable endocardial lead of FIG. 1Aor FIG. 1B.

FIG. 2A is an illustration of an embodiment of an implantableendocardial lead assembly, with a mapping stylet, and portions of anenvironment in which it is used.

FIG. 2B is an illustration of an embodiment of an apparatus for locatingthe His bundle by electrophysiological mapping using the implantableendocardial lead assembly of FIG. 2A.

FIG. 3 is an illustration of an embodiment of a cardiac rhythmmanagement system including the implantable endocardial lead of FIG. 1Aor FIG. 1B connected to an implantable pacemaker.

FIG. 4A is an illustration of an embodiment of an implantableendocardial lead assembly, with a needle, and portions of an environmentin which it is used.

FIG. 4B is an illustration of an embodiment of an apparatus fordelivering a biopacemaker therapy using the implantable endocardial leadassembly of FIG. 4A.

FIG. 5 is a flow chart illustrating a method for treating a heart by abiopacemaker therapy.

FIG. 6A is an illustration of a specific embodiment of the distal end ofthe implantable endocardial lead of FIG. 1B.

FIG. 6B is another illustration of the specific embodiment of the distalend of the implantable endocardial lead of FIG. 1B.

FIG. 7 is an illustration of a specific embodiment of the proximal endof the implantable endocardial lead of FIG. 1B.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings which form a part hereof, and in which is shown byway of illustration specific embodiments in which the invention may bepracticed. These embodiments are described in sufficient detail toenable those skilled in the art to practice the invention, and it is tobe understood that the embodiments may be combined, or that otherembodiments may be utilized and that structural, logical and electricalchanges may be made without departing from the spirit and scope of thepresent invention. The following detailed description provides examples,and the scope of the present invention is defined by the appended claimsand their equivalents.

It should be noted that references to “an”, “one”, or “various”embodiments in this disclosure are not necessarily to the sameembodiment, and such references contemplate more than one embodiment.

This document discusses, among other things, a cardiac rhythm management(CRM) system including an implantable endocardial lead assembly allowingdelivery of electrical therapy, chemical therapy, and biological therapyto an intracardiac region in or about the His bundle. However, it is tobe understood that the present methods and apparatuses may be employedto deliver electrical therapy, chemical therapy, and/or biologicaltherapy to other internal organs or regions of a person, including, butnot being limited to, other intracardiac regions. After an AV blockresulted from an injury to the AV node and/or the His bundle, pacing anddrug therapies are delivered to the intracardiac region in or about theHis bundle to prevent the His bundle degeneration, prevent theremodeling of the ventricular walls, and maintain a normal or at leasttolerable hemodynamic performance. The implantable endocardial leadassembly includes a lead and a mapping stylet for locating of theintracardiac region by electrophysiological mapping, and subsequently,delivering drug and/or electrical therapies to the located intracardiacregion. After the intracardiac region has been stabilized and/orconditioned by the drug and/or electrical therapy, a biological therapyis delivered to the intracardiac region to restore the ventricularrhythm that provides for a desirable hemodynamic performance.

The drug therapy includes delivering a pharmaceutical substance to theintracardiac region in or about the His bundle. In one embodiment, thedrug therapy conditions the His bundle to facilitate the biologicaltherapy. In one specific embodiment, the pharmaceutical substanceprevents the degeneration of the His bundle that occurs when AVconduction is absent. In another embodiment, the drug therapy, or anadditional drug therapy, is delivered subsequent to the biologicaltherapy to enhance the biological therapy. The pharmaceutical substanceincludes one or more chemical agents. In one example, a growth factor isdelivered to promote vessel growth in the intracardiac region, therebyincreasing blood supply to that region.

The electrical therapy includes His bundle pacing, i.e., deliveringcardiac pacing pulses to the intracardiac region in or about the Hisbundle. In one embodiment, the His bundle pacing conditions theintracardiac region to facilitate the biological therapy. In onespecific embodiment, the His bundle pacing prevents the degeneration ofthe His bundle and maintains its normal electrical conductioncharacteristics. In one embodiment, the His bundle pacing enhances thedrug therapy. In a further embodiment, the His bundle pacing isdelivered subsequent to the biological therapy to enhance the biologicaltherapy. Additionally, the His bundle pacing maintains or improveshemodynamic performance of the heart, such as increasing stroke volumeand ventricular synchrony, at least until the biological therapy issuccessful. The maintained hemodynamic performance prevents ventricularremodeling and creates a physiological environment facilitating thebiological therapy. The pacing mode for the His bundle pacing isselected from all available single chamber, dual chamber, andmulti-chamber pacing modes, based on the need and the circumstances of aparticular patient. In one embodiment, VVI or VVIR mode pacing isdelivered to the intracardiac region with the His bundle treated as aventricular pacing site. In another embodiment, in which a normal sinusrhythm is present, an atrial tracking pacing mode, such as VDD, VDDR,DDD, and DDDR, is applied with the His bundle treated as a ventricularpacing site. Other standard and custom pacing modes may also be applied,depending on the need and circumstances of each individual patient.

The biological therapy includes delivering a therapeutic biologicalsubstance to the intracardiac region in or about the His bundle. In oneembodiment, the therapeutic biological substance includes a biologicpacemaker. In another embodiment, the therapeutic biological substancedevelops into a biologic pacemaker in the intracardiac region. Thetherapeutic biological substance includes one or more of cells,matrices, and gene products. More specifically, the therapeuticbiological substance includes, but is not limited to, one or more ofexogenous cells, a cloned pacemaker channel, cloned α or β subunits ofthe endogenous human pacemaker current (HCN2 or other HCN types), andstem cells containing HCN channel genes. Examples of such biologicaltherapy are discussed in Qu et al., J. Physiol., 526(3), 561–69 (2000),Qu et al., Circ. Res., 89(1), e8 –14(2001), Yu et al., Circ. Res.,88(12), e84–87 (2001), and Shi et al., Circ. Res., 85(1 ), e1–6 (1999)

Throughout this document, unless otherwise indicated, “intracardiacregion” refers to the intracardiac region in or about the His bundle (AVbundle) or bundle branches. The drug therapy, electrical therapy, andbiological therapy can be administrated each alone, in any combination,and/or in any order or sequence, depending on the particular need andconditions of an individual patient.

FIGS. 1A–D illustrate various embodiments of an implantable endocardiallead assembly. The lead assembly includes a steerable stylet 120suitable for locating the His bundle by electrophysiological mapping, ahollow needle 134 suitable for intracardiac injection of the therapeuticbiological substance, and an implantable endocardial pacing lead 100(shown by its various embodiments including lead 100A and 100B). Lead100 includes a lumen 114 accommodating a portion of stylet 120 or aportion of needle 134. Lumen 114 allows a stylet distal end 124 or aneedle distal end 138 to reach the intracardiac region through lead 100.In this document, unless indicated otherwise, the term “distal end”refers to the portion of lead 100, stylet 120, or needle 134 that is tobe disposed in the intracardiac region, and the term “proximal end”refers to the opposite end of lead 100, stylet 120, or needle 134.

FIG. 1A is an illustration of portions of lead 100A, which is oneembodiment of lead 100. Lead 100A is a screw-in, unipolar endocardiallead providing an electrical connection between the intracardiac regionand an implantable CRM device. Lead 100A includes an elongate lead body102 having a lead distal end 108A and a lead proximal end 116. At ornear lead distal end 108A, lead 100A includes an electrode 104, afixation helix 106, and an osmotic drug collar 110. At lead proximal end116, lead 100A includes a terminal pin 118. A conductor 112Aelectrically and mechanically connects electrode 104 and terminal pin118. Lumen 114 extends throughout lead 100A and has a proximal openingat lead proximal end 116 and a distal opening at lead distal end 108A.It accommodates at least a portion of a flexible elongate object, andallows an end portion of that flexible elongate object to enter theproximal opening and exit from the distal opening. In one embodiment,the implantable CRM device includes a pacemaker. Electrode 104 allowsthe pacemaker to sense cardiac electrical activities from and deliveringpacing pulses to the intracardiac region.

Lead 100A includes a conductor 112A formed by a multifilar wire coiledaround a major portion of lumen 114 and connecting electrode 104 andterminal pin 118. In one embodiment, fixation helix 106 is mechanicallyconnected to electrode 104. In a further embodiment, fixation helix 106is also electrically connected to electrode 104, and is therefore a partof electrode 104. In one embodiment, fixation helix 106 is a retractablefixation. It advances or retracts in a rotating motion when terminal pin118 is being rotated. The rotation is translated to fixation helix 106through conductor 112A.

FIG. 1B is an illustration of portions of lead 100B, which is anotherembodiment of lead 100. As illustrated in FIG. 1B, lead 100B is abipolar lead providing for two separate electrical connections betweenthe intracardiac region and an implantable CRM device. Terminal pin 118for lead 100B includes two separate conductive portions that allowelectrodes 104 and 105 to connect to the implantable CRM deviceseparately. Lead 100B includes a first conductor 112A and a secondconductor 112IB. First conductor 112A is formed by a multifilar wirecoiled around a major portion of lumen 114 and connecting electrode 104and a first conductive portion of terminal pin 118. Second conductor112B is formed by another multifilar wire coiled around a major portionof first conductor 112A and connecting electrode 105 and a secondconductive portion of terminal pin 118. A tubular insulation layer 103separates conductors 112A and 112B. In one embodiment, fixation helix106 is mechanically and electrically coupled to conductor 112A, andincludes a conductive tip forming electrode 105. In one embodiment,fixation helix 106 is a retractable fixation. It advances or retracts ina rotating motion when terminal pin 118 is being rotated. The rotationis translated to fixation helix 106 through conductor 112A.

Lumen 114 in lead 100 (100A or 100B) accommodates one of a portion ofstylet 120 and a portion of needle 134, for the purposes of allowingaccess to the intracardiac region by stylet distal end 124 or needledistal end 138, respectively. In one embodiment, lumen 114 has asubstantially uniform diameter throughout its length.

Drug collar 110 is incorporated into the distal end of lead 100 (distalend 108A of lead 100A or distal end 108B of lead 100B) and delivers thepharmaceutical substance including the one or more chemical agents. Inone embodiment, drug collar 110 includes a drug reservoir containing thepharmaceutical substance and a means for controlled delivery of thepharmaceutical substance. In another embodiment, drug collar 110includes the means for controlled delivery of the pharmaceuticalsubstance, and the implantable CRM device includes the drug reservoir,which is in fluid communication with drug collar 110 via a passageway111 within and extending through lead 100. In one embodiment, the meansfor controlled delivery includes an osmotic membrane such that thepharmaceutical substance is delivered by way of osmosis. One example ofa drug delivery system including the drug reservoir containing thepharmaceutical substance and the means for controlled delivery of thepharmaceutical substance is discussed in U.S. patent application Ser.No. 10/246,249, “DEVICES AND METHODS TO STIMULATE THERAPEUTICANGIOGENESIS FOR ISCHEMIA AND HEART FAILURE,” filed on Sep. 18, 2002,assigned to Advanced Cardiovascular Systems, Inc., which is incorporatedherein by reference in its entirety.

Examples of additional details about lead 100 such as lead 100A or 100Bare discussed below with reference to FIGS. 6A, 6B, and 7.

FIG. 1C is an illustration of an embodiment of stylet 120. Stylet 120 isa steerable mapping stylet including a mapping electrode 126 at styletdistal end 124, a connector 132 at stylet proximal end 130, a conductor128 electrically connecting mapping electrode 126 and connector 132, anda nonconductive shell 122 insulating at least a major portion ofconductor 128. In one embodiment, mapping electrode 126, connector 132,and conductor 128 include a single conductor. Stylet 120 includes aninsulated conductor with both distal and proximal ends exposed to allowelectrical connection. That is, mapping electrode 126 includes anon-insulated portion of conductor 128 at about stylet distal end 124,and connector 132 includes another non-insulated terminal portion ofconductor 128 at about stylet proximal end 130.

Examples of material of which nonconductive shell 122 is made include,but are not limited to, silicone, polyurethane, Teflon, andpolytetrafluoroethylene (PTFE). Examples of material of which conductor128 and connector 132 are each is made include, but are not limited to,stainless steel and alloys of nickel, titanium, cobalt, etc. Examples ofmaterial of which electrode 126 is made include, but are not limited to,one or more of platinum and iridium alloy.

FIG. 1D is an illustration of an embodiment of a needle 134. Needle 134is a hollow needle that allows for intracardiac injection of thepharmaceutical and/or therapeutic biological substance. Needle 134includes a needle tip 140 at needle distal end 138, a needle connector146 at needle proximal end 144, a flexible needle body 136 connectingneedle tip 140 and needle connector 146, and a needle lumen 142extending throughout needle 134 to allow passage of the pharmaceuticaland/or therapeutic biological substance. In one embodiment, needle 134includes a radiopaque marker 139 at needle distal end 138 to allowmonitoring of the location of needle tip 140 inside a body usingfluoroscopy.

In one embodiment, needle tip 140 is constructed of, by way of example,but not by way of limitation, one of stainless steel, stainless steelalloys, and nitinol. Needle body 136 is constructed of, by way ofexample, but not by way of limitation, one of Teflon, polyethyleneterephthalate (PET), and polyurethane. Needle tip 140 includes anon-cutting tip, such as a conical tip, that is designed to avoiddamages to lumen 114 of lead 100.

In one embodiment, needle lumen 142 has a substantially uniform diameterthroughout its length. The diameter of needle lumen 142 is sufficientfor the passage of the pharmaceutical and/or therapeutic biologicalsubstance.

FIG. 2A is an illustration of an embodiment of an implantableendocardial lead assembly 252, including lead 100 and stylet 120, andportions of an environment in which it is used. In the drawing of thisdocument, lead 100 includes a pacing lead such as lead 100A and lead100B, and lead distal end 108 includes the distal end portion of lead100, such as lead distal end 108A of lead 100A and lead distal end 108Bof lead 100B, as discussed above with reference to FIGS. 2A and 2B. Leadassembly 252 is used for locating the His bundle in a heart 250 byelectrophysiological mapping. The mapping allows the electrical therapyand the drug therapy to be delivered directly to the His bundle byaccurately locating it. In FIG. 2A, lumen 114 of lead 100 accommodates aportion of stylet 120. Lead distal end 108 is disposed in a heart 250near the His bundle. Stylet 120 is steered to move forward and backwardrelative to lead 100, through lumen 114 of lead 100, such that mappingelectrode 126 is disposed outside of lead distal end 108 in a pluralityof sites within the intracardiac region.

FIG. 2B is an illustration of an embodiment of an apparatus for locatingthe His bundle by electrophysiological mapping using lead assembly 252.The electrophysiological mapping includes a process of seeking a sitewhere an electrical impulse as recorded from that site displays a knowntiming, amplitude, and/or morphological relationship with thatelectrical impulse as recorded from a known site. FIG. 2B illustrates anembodiment in which the His bundle is located by recording a His bundleelectrogram as well as atrial and/or ventricular electrogram. The atrialand/or ventricular electrograms are used as references for the timing,amplitude, or morphological relationship between an event in the Hisbundle electrogram and the same event in the atrial and/or ventricularelectrograms. In one specific embodiment, the drug and electricaltherapies are delivered after an AV node ablation in a patient sufferingatrial fibrillation. The His bundle is located by mapping before theablation, when the AV conduction is still intact, and the His bundle canbe located based on the known or expected conduction intervals betweenthe atrium and the His bundle and between His bundle and the ventricle.In another specific embodiment, the His bundle is located subsequent toan AV block based on a retrograde Purkinje fibers-His bundle conduction.

In FIG. 2B, a mapping system includes lead assembly 252 (including lead100 and stylet 120), an atrial lead 254 having at least one electrode inRA, and a ventricular lead 256 having at least one electrode in RV.Stylet 120, atrial lead 254, and ventricular lead 256 are connected to acardiac signal monitor 260 that senses electrograms. One specificexample of cardiac signal monitor 260 includes PRUCKA Cardio Lab EPSystem (model C-Lab Pro-800, GE Marquette Medical System). Cardiacsignal monitor 260 includes a display 262 to present an RA electrogram264A sensed via atrial lead 254, a His bundle electrogram 264B sensedvia stylet 120, and an RV electrogram 264C sensed via ventricular lead256. RA electrogram 264A includes events 266A indicative of RAdepolarizations, referred to as RA events. RV electrogram 264C includesevents 266C indicative of RV depolarizations, referred to as RV events,which are triggered by the electrical impulses which cause events 266Aand are conducted through the His Bundle to the RV. His bundleelectrogram 264B includes events 266B indicative of the AV conduction ofthe electrical impulses which cause events 266A, as recorded at thelocation of mapping electrode 126. In one embodiment, His bundleelectrogram 264B includes A, H, and V waves. The A waves correspond tothe RA depolarizations sensed by mapping electrode 126. The V wavescorrespond to the RV depolarizations sensed by mapping electrode 126.The H waves are events 266B. As illustrated in FIG. 2B, A, H, and Vwaves are identifiable by using the simultaneously displayed RAelectrogram 264A and/or RV electrogram 264C as references. Stylet 120provides for sensing of electrogram 264B in several sites in the generalarea where His bundle is likely located. In one embodiment, severalpairs of conduction intervals are measured, with respect to the severalsites, between adjacent events 266A and 266B, and between adjacentevents 266B and 266C. The His bundle, or the site for delivering theintended pacing and drug therapy, is located by identifying one pair ofthe conduction intervals that agrees with the expected RA-His bundleconduction interval and His Bundle-RV conduction interval. In anotherembodiment, several conduction intervals are measured, with respect tothe several sites, between adjacent events 266B and 266C. The Hisbundle, or the site for delivering the intended pacing and drug therapy,is located by identifying one of the conduction intervals that agreeswith the expected His bundle-RV conduction interval. In one specificembodiment, an AV conduction interval is measured between RA and RV. Inan alternative embodiment, ventricular lead 256 is disposed in heart 250with at least one electrode in LV. All the embodiments discussed withrespect to RV are applicable with RV substituted by LV. In one specificembodiment, an AV conduction interval is measured between RA and LV. Inone embodiment, amplitudes of events 266B measured at the several sitesare compared for locating or confirm the location of the His bundle. Theone of the several sites associated with the largest events 266Bamplitude is considered in or closest to the His bundle.

The atrium-His bundle conduction interval is generally expected to beabout 60 ms to 120 ms. The His bundle-ventricle conduction interval isgenerally expected to be about 35 ms to 55 ms.

FIG. 3 is an illustration of an embodiment of a CRM system includinglead 100 connected to an implantable device 370 that provides for apacing therapy. Implantable device 370 communicates with an externalsystem 372 via a telemetry link 374. Implantable device 370 includes acardiac pacemaker. In one embodiment, implantable device furtherincludes a defibrillator. In one embodiment, external system 372includes a programmer. In another system, external system 372 includesan advanced patient monitoring system such as discussed in U.S. patentapplication Ser. No. 10/323,604, “ADVANCED PATIENT MANAGEMENT FORDEFINING, IDENTIFYING AND USING PREDETERMINED HEALTH-RELATED EVENTS,”filed on Dec. 18, 2002, assigned to Cardiac Pacemakers, Inc., thespecification of which is incorporated herein by reference in itsentirety.

After the site for delivering the drug and/or electrical therapies islocated, fixation helix 106 of lead 100 is screwed in to that site byrotating terminal pin 118, and stylet 120 is removed from lead 100. Lead100 is then connected to implanted device 370 to allow the His bundlepacing. If the pacing mode used for the His bundle pacing requires RAsensing and/or pacing, atrial lead 254 remains connected to heart 250and is also connected to implantable medical device 370. If the pacingmode used for the His bundle pacing requires RV or LV sensing and/orpacing, ventricular lead 256 remains connected to heart 250 and is alsoconnected to implantable medical device 370.

In one embodiment, implantable device 370 includes a single chamberpacemaker capable of delivering VVI mode pacing (with the His bundletreated as a ventricular pacing site). In one further embodiment,implantable device 370 also includes a physiological sensor, such as anaccelerometer or a respiration sensor, to support a rate adaptive pacingin the VVIR mode. In one embodiment, implantable device 370 includes adual chamber or multi-chamber pacemaker capable of delivering eithersingle chamber pacing such as VVI mode pacing or dual/multi-chamberpacing such as VDD and DDD mode pacing. In one further embodiment,implantable device 370 also includes a physiological sensor, such as anaccelerometer or a respiration sensor, to support a rate adaptive pacingin pacing modes such as VVIR, VDDR, and DDDR. In one embodiment, thepacemaker includes other standard or custom pacing modes, to be selectedbased on the need and the circumstances of each individual patient.

The drug therapy is delivered by osmotic drug collar 110 at the distalend of lead 100. This includes releasing the pharmaceutical substance tothe area surrounding osmotic drug collar 110, i.e., the intracardiacregion in or near the His bundle. In one embodiment, the drug therapyenhances the therapeutic effect of the electrical therapy inconditioning the heart to facilitate an anticipated biological therapy.In another embodiment, the electrical therapy enhances the therapeuticeffect of the drug therapy.

FIG. 4A is an illustration of an embodiment of an implantableendocardial lead assembly 458, including lead 100 and needle 134, andportions of an environment in which it is used. Lead assembly 458 isused for delivering the biological therapy to the intracardiac region inor about the His bundle. The delivery of the biological therapy includesinjecting the biologic substance through needle 134. After the Hisbundle is located by the electrophysiological mapping, lead 100 is fixedto the site to which the drug therapy and/or the electrical therapy, aswell as the biological therapy, are delivered. To inject the biologicalsubstance, needle 134 is advanced through lumen 114 of lead 100 untilneedle tip 140 extends beyond lead distal end 108 of lead 100 to entercardiac tissue. In one embodiment, the needle tip is advanced to apredetermined point that is visible under fluoroscopy. In anotherembodiment, lead 100 and/or needle 134 include a needle stop structureto limit the extent to which needle tip can be extended beyond leaddistal end 108. The biologic substance is then injected into needleproximal end 144 and forced through needle 134 to enter the intracardiacsite.

FIG. 4B is an illustration of an embodiment of an apparatus fordelivering the biological therapy using lead assembly 458, includinglead 100 and needle 134. In one embodiment, after the intracardiacregion is treated by the drug and/or electrical therapies, thebiological therapy is delivered to the intracardiac region surroundinglead distal end 108 of lead 100. In one embodiment, lead 100 istemporarily disconnected from implantable device 370 for the delivery ofthe biological therapy. Needle 134 is then advanced through lumen 114until needle tip 140 penetrates into the tissue of the intracardiacregion. Needle connector 144 is connected to a biological therapyadministrator 480 from which the biological substance is delivered. Inone embodiment, biological therapy administrator 480 includes a syringe.

In one embodiment, the purpose of delivering the biological therapy isto develop a biologic pacemaker in the intracardiac region in or aboutthe His bundle in heart 250. This biologic pacemaker generateselectrical impulses in a way similar to the SA node. The His bundleconducts the electrical impulses from the biologic pacemaker to theright bundle branch (RBB) and left bundle branch (LBB). The RBB and LBBthen conduct the electrical impulses to the RV and LV, respectively,resulting in the synchronized contraction of the ventricles.

In one embodiment, after the delivery of the biological therapy, a drugtherapy and/or an electrical therapy is delivered using the CRM systemillustrated in FIG. 3. In one embodiment, after the delivery of thebiological therapy, the CRM system remains in the patient and continuesto deliver the drug and/or electrical therapies to the patient. The drugand/or electrical therapies enhance the biological therapy bystimulating the injected biological substance and by maintaining anintracardiac environment facilitating the development of the biologicpacemaker.

FIG. 5 is a flow chart illustrating a method for treating heart 250using combined drug, electrical, and biological therapies. The methodincludes delivering the drug, electrical and/or biological therapies tothe intracardiac region in or about the His bundle. Anelectrophysiological mapping is performed to locate the intracardiacregion at 500. In one embodiment, the intracardiac region is located byusing, for example, the apparatus illustrated in FIG. 2B, before an AVnode ablation. Mapping electrode 126 is placed in a plurality of sitesaccessible with lead assembly 252. One site suitable for delivering thedrug, electrical, and biological therapies, either being in the Hisbundle or the closest to the His bundle, is selected based on theamplitude and/or the timing of the electrical impulses recorded for eachof the plurality of sites.

The drug therapy is delivered to the located intracardiac region at 510.In one embodiment, a pharmaceutical substance is delivered from osmoticdrug collar 110 at lead distal end 108 of lead 100. The pharmaceuticalsubstance treats the intracardiac region to facilitate the biologicaltherapy.

The electrical therapy is delivered to the located intracardiac regionat 520. In one embodiment, the electrical therapy includes His bundlepacing. In one embodiment, pacing pulses are delivered from implantabledevice 370 via lead 100.

The biological therapy is delivered to the located intracardiac regionat 530. In one embodiment, a biological substance is delivered with leadassembly 458, i.e., through needle 134 advanced to the intracardiacregion through lumen 114 of lead 100.

The drug, electrical, and biological therapies can be performed indifferent orders and may each be repeated after interruption, dependingon each individual patient's needs and specific circumstances. In otherwords, steps 510, 520, and 530 in FIG. 5 do not denote any particularorder or sequence. For example, before the biological therapy, the drugtherapy and the electrical therapy can be delivered to condition thetissue to facilitate the biological therapy. After the biologicaltherapy is delivered, the drug therapy and the electrical therapy can bedelivered to enhance the biological therapy.

FIGS. 6A and 6B are detailed illustrations of one embodiment of thedistal end of a bipolar pacing lead 600 as a specific embodiment of lead100B. The design and construction of lead 600, including its detailedcomponents, are generally applicable for lead 100A, with necessarymodifications. FIG. 6A illustrates lead distal end 608 when lead 600 isin a retracted position. FIG. 6B illustrates a lead distal end 608 whenlead 600 is in an extended position. As illustrated in FIGS. 6A and 6B,lead 600 includes a tip electrode and a ring electrode. The tipelectrode includes a fixation helix 606, an electrode base 672, and anelectrode collar 678 connecting fixation helix 606 and electrode base672. Electrode base 672 and electrode collar 678 each have a tubularstructure forming a portion of lumen 614. Fixation helix 606 allows leaddistal end 608 to be affixed to the intracardiac region. Electrode base672 is mechanically connected to conductor a 612A, such that whenconductor 612A rotates, the electrode base 672 translates along an axis660 of lead 600. In a further embodiment, electrode base 672 is formedof an electrically conductive material, such as metal, and iselectrically connected to conductor 612A. Disposed about electrode base672 are external threads 676, which allow electrode base 672 to rotateand translate fixation helix 606. Electrode base 672 is coupled with anouter threaded shell 674. The ring electrode includes electrode 675,which is electrically connected to a conductor 612B. An inner insulation677 electrically insulates conductors 612A and 612B from each other. Alead body 602 provides for an outer insulation for the conductors.

In one embodiment, components of the tip and ring electrodes are allmade of conductive materials such as metals. Examples of material ofwhich fixation helix 606 is made include, but are not limited to,stainless steel, platinum-iridium, and titanium. Examples of material ofwhich electrode base 672 is made include, but are not limited to,stainless steel alloys. Examples of material of which electrode collar678 is made include, but are not limited to, stainless steel andplatinum-iridium alloys. Examples of material of which electrode 675 ismade include, but are not limited to, platinum-iridium alloys.

Lead 600 includes a drug collar 610 for delivering a pharmaceuticalsubstance including the one or more chemical agents. In one embodiment,drug collar 610 includes a drug reservoir containing the pharmaceuticalsubstance and a means for controlled delivery of the pharmaceuticalsubstance. In another embodiment, drug collar 610 includes the means forcontrolled delivery of the pharmaceutical substance. Lead 600 includes apassageway providing for fluid communication between drug collar 610 andthe implantable medical device to which lead 610 is connected.

Lead body 602 forms the outer shell for a major portion of lead 600.Examples of material of which the outer shell is made include, but arenot limited to, silicone and polyurethane.

In one embodiment, conductors 612A and 612B each include a coiledmultifilar wire. Examples of material of which the coiled multifilarwire is made include, but are not limited to, stainless steel, stainlesssteel alloy MP35N, titanium, and tantalum.

In one embodiment, a steroid collar 662 is disposed within lead distalend 608 of the lead 600. Steroid collar 662 includes a steroidalsubstance that releases into the intracardiac region after lead distalend 608 is placed in that region. The steroidal substance reducesinflammation that is a response to the invasion of lead 600 into theintracardiac region.

Outer threaded shell 674 includes internal threads 682. As the electrodebase 672 rotates, external threads 676 engage with internal threads 682and translate electrode base 672 along axis 660. In one embodiment, lead600 includes a stop to prevent fixation helix 606 from over-extension.In one embodiment, a stop 670 on internal threads 682 blocks therotation of external threads 676. Once external threads 676 reach stop670, electrode base 672 can no longer be rotated and translated. Thisprevents fixation helix 606 from being over-extended into the tissue ofthe intracardiac region. In one embodiment, a stop 666 is formed on anouter shell 680 to block the movement of electrode collar 678.

In one embodiment, outer threaded shell 674 and/or outer shell 680 areeach formed of polyetheretherketone (PEEK). In one embodiment, outerthreaded shell 674 is formed of PEEK 150G, which has a low meltviscosity. For PEEK 150G, the melt viscosity ranges from about 0.12–0.18KNs/m², and the tensile strength is greater than or equal to 90 MPa. Inanother embodiment, outer threaded shell 674 is formed of PEEK 450G,which has a standard melt viscosity. For PEEK 450G, the melt viscosityranges from about 0.38–0.50 KNs/m², and the tensile strength is greaterthan or equal to 90 MPa. PEEK allows outer threaded shell 674 to bemolded, extruded, or machined for tighter tolerances or providingprecision structures. PEEK is a tough rigid thermoplastic material thatis biocompatible.

Proximate to lead distal end 608 of lead 600 is a fluoroscopy ring 664,as a radiopaque marker disposed about fixation helix 106. In oneembodiment, as fixation helix 606 is extended out from lead 600,electrode collar 678 translates toward fluoroscopy ring 664 untilabutting a portion fluoroscopy ring 664, at which point the fixationhelix 606 is fully extended. Electrode collar 678 and fluoroscopy ring664 allow viewing, under fluoroscopy, of whether fixation helix 606 isfully extended.

In one embodiment, outer shell 680 provides a stop for the translationof electrode collar 678. Outer shell 680 is coupled with outer threadedshell 674. In one embodiment, epoxy 668 is disposed between outerthreaded shell 674 and outer shell 680. In one embodiment, epoxy 668includes a blend of two different epoxies. The two different epoxiesinclude EPOTEK® 353ND and EPOTEK® 353ND-T made by Epoxy Technology. Theyare mixed in the ratio of 1 part EPOTEK® 353ND to 1.75 parts EPOTEK®353ND-T. Epoxy 668 is cured at a temperature of 150° C. for one hour.

FIG. 7 is a detailed illustration of one embodiment of a lead proximalend 716 of lead 600 (as a specific embodiment of lead 100B). Leadproximal end 716 includes a terminal pin 718, which is mechanically andelectrically coupled to conductor 612A. Terminal pin 718 provides theelectrical connection between implantable device 370 and the tipelectrode of lead 600 though conductor 612A. A connective crimp tube 787reinforces the connection between terminal pin 718 and conductor 612A.As terminal pin 718 is rotated, conductor 612A rotates, thereby rotatingelectrode base 672, electrode collar 678, and fixation helix 606.Terminal pin 718 has a tubular structure that forms a proximal portionof lumen 614.

Lead 600 further includes an outer terminal ring 796 that iselectrically coupled to conductor 612B through a conductive collar 789to provide the electrical connection between implantable device 370 andthe ring electrode (675) of lead 600 though conductor 612B. An insulatorsleeve 798 is disposed over at least a portion of terminal pin 718, toinsulate terminal pin 718 from outer terminal ring 796. In oneembodiment, sleeve 798 rotates with outer terminal ring 796. In oneembodiment, sleeve 798 is coupled to terminal pin 718 with a snap-fitconnection. In another embodiment, sleeve 798 is also coupled to outerterminal ring 796 with a snap-fit connection. In one embodiment, sleeve798 includes a shoulder 790. Shoulder 790 is engaged with a recess 794of terminal pin 718, and prevents terminal pin 718 from moving axially.In one embodiment, shoulder 790 includes an annular shoulder disposedabout the circumference of sleeve 798, which allows terminal pin 718 torotate relative to outer terminal ring 796. The annular shoulder engageswithin an annular recess disposed within the circumference of terminalpin 718. In another embodiment, sleeve 798 further includes at least onerecess 788 disposed adjacent to shoulder 790. Recess 788 receives ashoulder 786 of terminal pin 718. In another embodiment, sleeve 798further includes a stop 792 for outer terminal ring 796. Terminal pinbody 791 provides increased axial strength to the connection betweenlead 600 and implantable device 370.

Terminal pin 718 and outer terminal ring 796 are each made of conductivematerials such as metals. Examples of material of which terminal pin 718is made include, but are not limited to, stainless steel, titanium, andplatinum-iridium. Examples of material of which terminal ring 796 ismade include, but are not limited to, stainless steel, titanium, andplatinum-iridium.

Sleeve 798 is formed of non-conductive material. In one embodiment,sleeve 798 is formed of PEEK. In one embodiment, sleeve 798 is formed ofPEEK 150G. In another embodiment, sleeve 798 is formed of PEEK 450G. ThePEEK allows sleeve 798 to be molded, extruded, or machined for tightertolerances or providing precision structures.

Lumen 614 extends along axis 600 throughout lead 600, and has asubstantially circular cross-section perpendicular to axis 600. Asillustrated in FIGS. 6A, 6B, and 7, lumen 614 is formed directly by thetip electrode of lead 600, conductor 612, and terminal pin 718. Lumen614 has a distal opening at lead distal end 608 and a proximate openingat lead proximal end 616. In one embodiment, the substantially circularcross-section has a substantially uniform diameter throughout lead 600.The diameter is of a size allowing passage of stylet 120 and needle 134(one at a time).

Generally, metals used for components of lead 600, as illustrated inFIGS. 6A. 6B, and 7, include, but are not limited to, stainless steel,titanium, niobium, platinum-iridium alloys, other alloys such as elgiloyand nickel/titanium alloys. Non-metal materials used for components oflead 600, as illustrated in FIGS. 6A. 6B, and 7, include, but are notlimited to, silicone, polyurethane, polydimethyls, siloxanes, and PEEK.

Other embodiments of the detailed structure and elements of lead 600 areavailable by adopting and/or modifying existing lead structures andelements to include lumen 614. Examples of such existing lead structuresand elements are discussed in U.S. Pat. No. 6,141,594, “SINGLE PASS LEADAND SYSTEM WITH ACTIVE AND PASSIVE FIXATION ELEMENTS,” U.S. Pat. No.6,463,334, “EXTENDABLE END RETRACTABLE LEAD,” U.S. patent applicationSer. No. 10/264,494, “EXTENDABLE AND RETRACTABLE LEAD HAVING A SNAP-FITTERMINAL CONNECTOR,” filed Oct. 4, 2002, all assigned to CardiacPacemakers, Inc., which are incorporated herein by reference in theirentirety.

It is to be understood that the above detailed description is intendedto be illustrative, and not restrictive. Other embodiments will beapparent to those of skill in the art upon reading and understanding theabove description. The scope of the invention should, therefore, bedetermined with reference to the appended claims, along with the fullscope of equivalents to which such claims are entitled.

1. An implantable endocardial lead adapted for use with an implantablecardiac rhythm management device including a drug reservoir, the leadcomprising: an implantable elongate lead body having a proximal end anda distal end, the proximal end configured to be connected to theimplantable cardiac rhythm management device; an implantable electrodeat or near the distal end for sensing cardiac electrical activities anddelivering pacing pulses; a lumen within and extending through the leadbody, the lumen having a proximal opening at about the proximal end anda distal opening at about the distal end, the lumen adapted toaccommodate at least a portion of a flexible elongate object and toallow an end portion of the flexible elongate object to enter theproximal opening and extend from the distal opening; an implantable drugdelivery device including a drug collar positioned away from the lumenat or near the distal end, the implantable drug delivery device adaptedto deliver a pharmaceutical substance; a passageway extending throughthe implantable elongate lead body and configured to provide fluidcommunication between the drug collar and the drug reservoir; and afixation helix at the distal end.
 2. The lead of claim 1, wherein theimplantable electrode comprises the fixation helix.
 3. The lead of claim2, further comprising a terminal pin at the proximal end.
 4. The lead ofclaim 3, further comprising a conductor within and extending through thelead body, the conductor connected to the electrode and the terminal pinand allowing rotation of the fixation helix upon by rotating theterminal pin.
 5. The lead of claim 4, wherein the conductor comprises amultifilar wire coiled around the lumen.
 6. The lead of claim 1, whereinthe implantable drug delivery device comprises an osmotic membrane and adrug reservoir containing the pharmaceutical substance.
 7. The lead ofclaim 1, wherein the pharmaceutical substance comprises one or moreagents preventing a degeneration of a cardiac conduction system.
 8. Thelead of claim 7, further comprising a steroid collar disposed within thedistal end, the steroid collar including a steroidal substance thatreduces inflammation.
 9. The lead of claim 1, wherein the implantableelectrode comprises an electrode collar forming a portion of the lumen.10. An implantable endocardial pacing lead assembly for use with animplantable device including a drug reservoir, the lead assemblycomprising: a hollow needle adapted for intracardiac injection of atherapeutic biological substance, the needle including; a needle tip;and a flexible needle body connected to the needle tip; and animplantable lead including: an elongate lead body having a lead proximalend and a lead distal end the lead proximal end configured to beconnected to the implantable device; an electrode at or near the leaddistal end for sensing cardiac electrical activities and deliveringpacing pulses; a lumen within and extending through the lead body, thelumen including an proximal opening at about the lead proximal end and adistal opening at about the lead distal end, the lumen adapted toaccommodate at least a portion of the needle and to allow the needle tipto enter the proximal opening and extend from the distal opening; a drugdelivery device including a drug collar positioned away from the lumenat or near the distal end, the drug delivery device adapted to deliver apharmaceutical substance; and a passageway extending through theimplantable elongate lead body and configured to provide fluidcommunication between the drug collar and the drug reservoir.
 11. Thelead assembly of claim 10, wherein the hollow needle comprises aradiopaque marker at or near the needle tip, to allow fluoroscopicmonitoring.
 12. The lead assembly of claim 11, wherein the hollow needlecomprises a lumen having a substantially circular cross-section and adiameter suitable for delivery of a biologic pacemaker matrix.
 13. Thelead assembly of claim 11, wherein the hollow needle comprises a lumenhaving a substantially circular cross-section and a diameter suitablefor delivery of exogenous cells.
 14. The lead assembly of claim 11,wherein the hollow needle comprises a lumen having a substantiallycircular cross-section and a diameter suitable for delivery of a growthfactor.
 15. The lead assembly of claim 11, wherein the hollow needlecomprises a lumen having a substantially circular cross-section and adiameter suitable for delivery of a cloned biologic pacemaker channel.16. The lead assembly of claim 10, wherein the drug delivery devicecomprises an osmotic membrane and a drug reservoir containing thepharmaceutical substance.
 17. The lead assembly of claim 16, wherein thepharmaceutical substance comprises one or more agents conditioning acardiac conductive system before the intracardiac injection of thetherapeutic biological substance.
 18. The lead of claim 10, wherein theimplantable lead comprises: a further electrode at or near the leaddistal end for sensing cardiac electrical activities and deliveringpacing pulses; and a fixation helix at the lead distal end, the fixationhelix forming a portion of one of the electrode and the furtherelectrode.
 19. The lead of claim 10, wherein the flexible needle bodycomprises one of Teflon, polyethylene, and terephthalate (PET).